Avoid the impact of trial supply shortages and scarcity across the life of your trial

There has been an increase in drug shortages, which has impacted clinical trials, caused by a range of factors, including disruptions to manufacturing, stricter regulations, and increased demand.

Industry-wide concern with supply chain vulnerabilities and scarcity of critical medicines has increased so much over recent years that the European Commission has launched an Alliance to focus on shortages [1]. Oncology trials are especially impacted, with reported shortages of many Standard of Care treatments [2].

Whether lack of drug availability is unexpected and temporary, due to a lot manufacturing delay, or known, and a widespread industry concern, such as comparator sourcing, making the best use of flexible IRT inventory management avoids impacts to planning, site supply, and participant dosing.

There are proactive steps you can take to mitigate associated risks, as great RTSM/IRT design can prevent shortages and scarcity from jeopardizing study goals.

What steps you can take depends on the supply challenge faced, but actions can be taken to manage both expected and emergency drug shortages when:

— Planning – supply simulation can assist with planning manufacturing campaigns and optimal supply chains, especially if supplies are limited
— Designing – advanced supply management options can ensure the challenge of limited stock is prioritized
— Adapting – RTSM settings can be quickly adapted to manage unforeseen situations during trial execution, such as delayed batch manufacture

Planning
By testing a design aspect/assumption, as well as various potential recruitment patterns, our in-house expert statistical design and trial supply consultants run a simulation to help sponsors make informed decisions about the quantity of medication to produce for use in clinical development.

Designing
When can you influence waste? The ability to influence the amount of drug wastage decreases as the trial progresses. We recommend engaging with RTSM design early on, during the protocol planning phase – protocol design impacts inventory management and considering supplies early leads to better control.

During trial set-up, IRT trial supply experts can recommend how to best meet your challenges, including drug availability and scarcity and carbon emission reduction. Our supply experts will help you make decisions about how to automatically optimize the use of limited supplies, manage sourcing changes, manage supplies across many global sites, and so on.

Your IRT should automatically manage each participant’s scheduled, predictable medication needs. Great design can also support unpredictable needs, such as if/when participants will be randomized, whether medication types will be needed for adaptive or multi-part trials, or sourcing changes. Advanced, tailored design can automatically adapt a site’s resupply strategy to events and milestones, such as recruitment rate, avoiding over-stocking sites which do not recruit or have a lower rate than expected.

Adapting
Inventory Management settings are agreed during start-up activities and should be based on protocol design, packaging plan, operational needs and any concerns, such as high shipment costs, short shelf-life, limited supply, substantial number of sites, unpredictable participant resupply needs and expensive drug. These settings should not be fixed; it should be possible to temporarily adapt them to react to new trial constraints or unforeseen situations, such as drug shortages or a delayed batch.

You need parameters which can be temporarily amended as and when needed to get the most use out of existing medication. You may be familiar with these terms:

— Do Not Dispense is set so kit/s assigned do not expire whilst in the participant’s possession, considering the number of doses in a kit. DND impacts the date until which a kit can be dispensed to a participant.

— Do Not Ship is set so kits are within expiry when reaching the site (and have sufficient shelf life to meet needs of participants’ upcoming scheduled visits). DNS impacts the number of participant visits the IRT predicts for, the quantity per shipment and the total number of shipments to sites.

These and other IRT system parameters can be adapted when you face challenges with medication availability, for example, when:

There is no replacement medication for an ongoing participant

Situation: For extreme situations where there is a risk of losing participants if they are not dosed.
Action:
— Extend the date by which a kit can be allocated to a participant: Adding a ‘Last Use By’ date could allow a kit to be allocated to a participant, even if the kit will expire in the participant’s possession. As this could lead to participant safety concerns, it must be a last resort and requires the site to pay close attention to when a participant should return to obtain new medication. It’s critical to consider the impact of every update to an inventory management setting and when those updates should be applied until; our RTSM experts can help you to understand the impact.

The release of a new batch is delayed

Situation: The current batch has stopped being shipped due to expiry checks and there is no batch with a later expiry date / relabeling has not yet been completed.
Action:
— Increase the amount of medication which can be sent from a depot to a site before it reaches expiry.
— Reduce the number of participant visits’ worth of medication included in each shipment to a site, only including medication for imminent participant visits.
— Extend the amount of time a batch can be shipped to a country.

Engage an expert early.
A good IRT/RTSM system can be used as a tool to support scarcity and availability issues with the right design and by amending different inventory management settings, alone or in combination. By amending the right settings in the right way, there will be an immediate impact on batch management, site shipments, and participant dispensation.

Our recommendation will always be to discuss with an IRT/RTSM expert who supports a range of challenges and who understands how the system can be both designed and adapted to address them.

Engage an IRT expert early to ensure you get the right help with your known shortages and scarcity concerns.
Ongoing engagement will ensure you solve any shortages efficiently and effectively so participants receive the treatment they need safely.

Author: Ashish Patel, Associate Director, Project & Program Management

References
[1[ Commission launches the Critical Medicines Alliance to help prevent and address shortages of critical medicines – European Commission
[2] Effects of Cancer Drug Shortages Linger as New Survey Results Show Impacts on Clinical Trials